)
Ranitidine (Zantac®) (Alteration in gastric pH) 150 mg (morning dose of 150 mg Ranitidine BID) ↑4%
(1.04; 0.88 -1.23)↑ ↓3%
(0.97; 0.84 -1.12)
Esomeprazole (Nexium®) (Increase in gastric pH) 40 mg (QAM 5 days, day -4 to 1) ↑2%
(1.02; 0.88-1.17)↑ ↑5%
(1.05; 0.89 -1.24)
Metoclopramide (Reglan®) (Increase in gastric motility) 15 mg four times daily during 2 days (Day -1 and 1) ↓14%
(0.86, 0.73,1.02) ↓7%
(0.93, 0.803,1.07)
Posaconazole oral suspension is absorbed with a median Tmax of ~3 to 5 hours. Steady-state plasma concentrations are attained at 7 to 10 days following multiple-dose administration.
Following single-dose administration of 200 mg, the mean AUC and Cmax of posaconazole are approximately 3-times higher when the oral suspension is administered with a nonfat meal and approximately 4-times higher when administered with a high-fat meal (~50 gm fat) relative to the fasted state. Following single-dose administration of posaconazole oral suspension 400 mg, the mean AUC and Cmax of posaconazole are approximately 3-times higher when administered with a liquid nutritional supplement (14 gm fat) relative to the fasted state (see Table 12). In addition, the effects of varying gastric administration conditions on the Cmax and AUC of posaconazole oral suspension in healthy volunteers have been investigated and are shown in Table 13.
In order to assure attainment of adequate plasma concentrations, it is recommended to administer Noxafil oral suspension during or immediately following a full meal. In patients who cannot eat a full meal, Noxafil oral suspension should be taken with a liquid nutritional supplement or an acidic carbonated beverage (e.g., ginger ale).
Table 12: The Mean (%CV) [min-max] Posaconazole Pharmacokinetic Parameters Following Single-Dose Oral Suspension Administration of 200 mg and 400 mg Under Fed and Fasted Conditions
Dose (mg)
Cmax
(ng/mL)
Tmax*
(hr)
AUC (I)
(ng∙hr/mL)
CL/F
(L/hr)
t½
(hr)
* Median [min-max].† n=15 for AUC (I), CL/F, and t ½ ‡ The subject with Tmax of 36 hrs had relatively constant plasma levels over 36 hrs (1.7 ng/mL difference between 4 hrs and 36 hrs).§ n=10 for AUC (I), CL/F, and t ½
200 mg fasted
(n=20)† 132 (50)
[45-267] 3.50
[1.5-36‡] 4179 (31)
[2705-7269] 51 (25)
[28-74] 23.5 (25)
[15.3-33.7]
200 mg nonfat
(n=20)† 378 (43)
[131-834] 4 [3-5] 10,753 (35)
[4579-17,092] 21 (39)
[12-44] 22.2 (18)
[17.4-28.7]
200 mg high fat
(54 gm fat)
(n=20)† 512 (34)
[241-1016] 5 [4-5] 15,059 (26)
[10,341-24,476] 14 (24)
[8.2-19] 23.0 (19)
[17.2-33.4]
400 mg fasted
(n=23)§ 121 (75)
[27-366] 4 [2-12] 5258 (48)
[2834-9567] 91 (40)
[42-141] 27.3 (26)
[16.8-38.9]
400 mg with liquid nutritional supplement
(14 gm fat)
(n=23)§ 355 (43)
[145-720] 5 [4-8] 11,295 (40)
[3865-20,592] 43 (56)
[19-103] 26.0 (19)
[18.2-35.0]
Table 13: The Effect of Varying Gastric Administration Conditions on the Cmax and AUC of Posaconazole Oral Suspension in Healthy Volunteers
Study Description
Administration Arms
Change in Cmax
(ratio estimate*;
90% CI of the ratio estimat
